68Ga-DOTA-Siglec-9

A new imaging tool to detect synovitis

Helena Virtanen, Anu Autio, Riikka Siitonen, Heidi Liljenbäck, Tiina Saanijoki, Petteri Lankinen, Jussi Mäkilä, Meeri Käkelä, Jarmo Teuho, Nina Savisto, Kimmo Jaakkola, Sirpa Jalkanen, Anne Roivainen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)

Abstract

Introduction: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule, which upon inflammation is rapidly translocated from intracellular sources to the endothelial cell surface. We have recently discovered that sialic acid- binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1 and that 68Ga-labeled Siglec-9 motif peptide facilitates in vivo imaging of inflammation. This study evaluated the feasibility of 68Ga-DOTA-Siglec-9 positron emission tomography (PET) for the assessment of synovitis. Methods: Rabbits with synovial inflammation were injected with 18F-FDG or 68Ga-DOTA-Siglec-9 and studied by gamma counting and autoradiography. Certain rabbits were also examined with magnetic resonance imaging (MRI). After PET imaging, rabbits were intravenously administered with anti-VAP-1 antibody to evaluate luminal expression of VAP-1 by immunohistochemistry. Finally, binding of Siglec-9 peptide and VAP-1 positive vessels were evaluated by double staining of rheumatoid arthritis synovium. Results: Intra-articular injection of hemagglutinin induced mild synovial inflammation in rabbit knee with luminal expression of VAP-1. Synovitis was clearly visualized by 68Ga-DOTA-Siglec-9 PET in addition to 18F-FDG-PET and MRI. Compared with the 18F-FDG, the ex vivo inflamed-to-control synovium ratio of 68Ga-DOTA-Siglec-9 was similar (1.7 ± 0.4 vs. 1.5 ± 0.2, P = 0.32). Double staining revealed that Siglec-9 peptide binds to VAP-1 positive vessels in human rheumatoid synovium. Conclusion: Ga-DOTA-Siglec-9 PET tracer detected VAP-1 positive vasculature in the mild synovitis of rabbits comparable with 18F-FDG, suggesting its potential for in vivo imaging of synovial inflammation in patients with rheumatic diseases.
Original languageEnglish
Article number308
JournalArthritis Research and Therapy
Volume17
DOIs
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

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Sialic Acid Binding Immunoglobulin-like Lectins
Synovitis
Blood Vessels
Positron-Emission Tomography
Fluorodeoxyglucose F18
Synovial Membrane
Rabbits
Inflammation
Proteins
Peptides
Magnetic Resonance Imaging
Staining and Labeling
Intra-Articular Injections
Hemagglutinins
Feasibility Studies
Rheumatic Diseases
Autoradiography
Rheumatoid Arthritis
Knee
Leukocytes

Keywords

  • Gallium-68
  • inflammation
  • PET
  • rabbit
  • vascular adhesion protein-1

Cite this

Virtanen, H., Autio, A., Siitonen, R., Liljenbäck, H., Saanijoki, T., Lankinen, P., ... Roivainen, A. (2015). 68Ga-DOTA-Siglec-9: A new imaging tool to detect synovitis. Arthritis Research and Therapy, 17, [308]. https://doi.org/10.1186/s13075-015-0826-8
Virtanen, Helena ; Autio, Anu ; Siitonen, Riikka ; Liljenbäck, Heidi ; Saanijoki, Tiina ; Lankinen, Petteri ; Mäkilä, Jussi ; Käkelä, Meeri ; Teuho, Jarmo ; Savisto, Nina ; Jaakkola, Kimmo ; Jalkanen, Sirpa ; Roivainen, Anne. / 68Ga-DOTA-Siglec-9 : A new imaging tool to detect synovitis. In: Arthritis Research and Therapy. 2015 ; Vol. 17.
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title = "68Ga-DOTA-Siglec-9: A new imaging tool to detect synovitis",
abstract = "Introduction: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule, which upon inflammation is rapidly translocated from intracellular sources to the endothelial cell surface. We have recently discovered that sialic acid- binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1 and that 68Ga-labeled Siglec-9 motif peptide facilitates in vivo imaging of inflammation. This study evaluated the feasibility of 68Ga-DOTA-Siglec-9 positron emission tomography (PET) for the assessment of synovitis. Methods: Rabbits with synovial inflammation were injected with 18F-FDG or 68Ga-DOTA-Siglec-9 and studied by gamma counting and autoradiography. Certain rabbits were also examined with magnetic resonance imaging (MRI). After PET imaging, rabbits were intravenously administered with anti-VAP-1 antibody to evaluate luminal expression of VAP-1 by immunohistochemistry. Finally, binding of Siglec-9 peptide and VAP-1 positive vessels were evaluated by double staining of rheumatoid arthritis synovium. Results: Intra-articular injection of hemagglutinin induced mild synovial inflammation in rabbit knee with luminal expression of VAP-1. Synovitis was clearly visualized by 68Ga-DOTA-Siglec-9 PET in addition to 18F-FDG-PET and MRI. Compared with the 18F-FDG, the ex vivo inflamed-to-control synovium ratio of 68Ga-DOTA-Siglec-9 was similar (1.7 ± 0.4 vs. 1.5 ± 0.2, P = 0.32). Double staining revealed that Siglec-9 peptide binds to VAP-1 positive vessels in human rheumatoid synovium. Conclusion: Ga-DOTA-Siglec-9 PET tracer detected VAP-1 positive vasculature in the mild synovitis of rabbits comparable with 18F-FDG, suggesting its potential for in vivo imaging of synovial inflammation in patients with rheumatic diseases.",
keywords = "Gallium-68, inflammation, PET, rabbit, vascular adhesion protein-1",
author = "Helena Virtanen and Anu Autio and Riikka Siitonen and Heidi Liljenb{\"a}ck and Tiina Saanijoki and Petteri Lankinen and Jussi M{\"a}kil{\"a} and Meeri K{\"a}kel{\"a} and Jarmo Teuho and Nina Savisto and Kimmo Jaakkola and Sirpa Jalkanen and Anne Roivainen",
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Virtanen, H, Autio, A, Siitonen, R, Liljenbäck, H, Saanijoki, T, Lankinen, P, Mäkilä, J, Käkelä, M, Teuho, J, Savisto, N, Jaakkola, K, Jalkanen, S & Roivainen, A 2015, '68Ga-DOTA-Siglec-9: A new imaging tool to detect synovitis', Arthritis Research and Therapy, vol. 17, 308. https://doi.org/10.1186/s13075-015-0826-8

68Ga-DOTA-Siglec-9 : A new imaging tool to detect synovitis. / Virtanen, Helena; Autio, Anu; Siitonen, Riikka; Liljenbäck, Heidi; Saanijoki, Tiina; Lankinen, Petteri; Mäkilä, Jussi; Käkelä, Meeri; Teuho, Jarmo; Savisto, Nina; Jaakkola, Kimmo; Jalkanen, Sirpa; Roivainen, Anne (Corresponding Author).

In: Arthritis Research and Therapy, Vol. 17, 308, 2015.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - 68Ga-DOTA-Siglec-9

T2 - A new imaging tool to detect synovitis

AU - Virtanen, Helena

AU - Autio, Anu

AU - Siitonen, Riikka

AU - Liljenbäck, Heidi

AU - Saanijoki, Tiina

AU - Lankinen, Petteri

AU - Mäkilä, Jussi

AU - Käkelä, Meeri

AU - Teuho, Jarmo

AU - Savisto, Nina

AU - Jaakkola, Kimmo

AU - Jalkanen, Sirpa

AU - Roivainen, Anne

PY - 2015

Y1 - 2015

N2 - Introduction: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule, which upon inflammation is rapidly translocated from intracellular sources to the endothelial cell surface. We have recently discovered that sialic acid- binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1 and that 68Ga-labeled Siglec-9 motif peptide facilitates in vivo imaging of inflammation. This study evaluated the feasibility of 68Ga-DOTA-Siglec-9 positron emission tomography (PET) for the assessment of synovitis. Methods: Rabbits with synovial inflammation were injected with 18F-FDG or 68Ga-DOTA-Siglec-9 and studied by gamma counting and autoradiography. Certain rabbits were also examined with magnetic resonance imaging (MRI). After PET imaging, rabbits were intravenously administered with anti-VAP-1 antibody to evaluate luminal expression of VAP-1 by immunohistochemistry. Finally, binding of Siglec-9 peptide and VAP-1 positive vessels were evaluated by double staining of rheumatoid arthritis synovium. Results: Intra-articular injection of hemagglutinin induced mild synovial inflammation in rabbit knee with luminal expression of VAP-1. Synovitis was clearly visualized by 68Ga-DOTA-Siglec-9 PET in addition to 18F-FDG-PET and MRI. Compared with the 18F-FDG, the ex vivo inflamed-to-control synovium ratio of 68Ga-DOTA-Siglec-9 was similar (1.7 ± 0.4 vs. 1.5 ± 0.2, P = 0.32). Double staining revealed that Siglec-9 peptide binds to VAP-1 positive vessels in human rheumatoid synovium. Conclusion: Ga-DOTA-Siglec-9 PET tracer detected VAP-1 positive vasculature in the mild synovitis of rabbits comparable with 18F-FDG, suggesting its potential for in vivo imaging of synovial inflammation in patients with rheumatic diseases.

AB - Introduction: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule, which upon inflammation is rapidly translocated from intracellular sources to the endothelial cell surface. We have recently discovered that sialic acid- binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1 and that 68Ga-labeled Siglec-9 motif peptide facilitates in vivo imaging of inflammation. This study evaluated the feasibility of 68Ga-DOTA-Siglec-9 positron emission tomography (PET) for the assessment of synovitis. Methods: Rabbits with synovial inflammation were injected with 18F-FDG or 68Ga-DOTA-Siglec-9 and studied by gamma counting and autoradiography. Certain rabbits were also examined with magnetic resonance imaging (MRI). After PET imaging, rabbits were intravenously administered with anti-VAP-1 antibody to evaluate luminal expression of VAP-1 by immunohistochemistry. Finally, binding of Siglec-9 peptide and VAP-1 positive vessels were evaluated by double staining of rheumatoid arthritis synovium. Results: Intra-articular injection of hemagglutinin induced mild synovial inflammation in rabbit knee with luminal expression of VAP-1. Synovitis was clearly visualized by 68Ga-DOTA-Siglec-9 PET in addition to 18F-FDG-PET and MRI. Compared with the 18F-FDG, the ex vivo inflamed-to-control synovium ratio of 68Ga-DOTA-Siglec-9 was similar (1.7 ± 0.4 vs. 1.5 ± 0.2, P = 0.32). Double staining revealed that Siglec-9 peptide binds to VAP-1 positive vessels in human rheumatoid synovium. Conclusion: Ga-DOTA-Siglec-9 PET tracer detected VAP-1 positive vasculature in the mild synovitis of rabbits comparable with 18F-FDG, suggesting its potential for in vivo imaging of synovial inflammation in patients with rheumatic diseases.

KW - Gallium-68

KW - inflammation

KW - PET

KW - rabbit

KW - vascular adhesion protein-1

U2 - 10.1186/s13075-015-0826-8

DO - 10.1186/s13075-015-0826-8

M3 - Article

VL - 17

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

SN - 1478-6354

M1 - 308

ER -

Virtanen H, Autio A, Siitonen R, Liljenbäck H, Saanijoki T, Lankinen P et al. 68Ga-DOTA-Siglec-9: A new imaging tool to detect synovitis. Arthritis Research and Therapy. 2015;17. 308. https://doi.org/10.1186/s13075-015-0826-8